Pulmonary Disfunction after Polysubstance Exposure: Mechanistic Identification of Inflammatory Mediators
Project Number5SC2GM144188-03
Contact PI/Project LeaderSIVARAMAN, VIJAY
Awardee OrganizationNORTH CAROLINA CENTRAL UNIVERSITY
Description
Abstract Text
Abstract
Alcohol and marijuana (cannabinoids) are commonly abused drugs worldwide, and adolescent
co-exposure/co-abuse of these two drugs is hallmarked by high levels of co-morbidity. Both chronic
binge ethanol and cannabinoid consumption enhances the risk of acute lung injury (ALI) and both
community and health care associated pneumonia (CAP and HAP, respectively), leading to increased
morbidity and mortality. We have recently utilized a mouse model for adolescent intermittent ethanol
(AIE) and cannabinoid (AIC) exposure to examine roles of binge exposure to adult-pulmonary
inflammation, and our data suggests that that the prior polysubstance exposure leads to increased
HMGB1 expression and microbial-induced pulmonary inflammation. Interestingly, our in vitro studies
indicate that both alcohol and cannabinoids activate HMGB-1 expression from macrophage cells, and
inhibiting cannabinoid receptors CB1R and CB2R on cells inhibits HMGB-1 expression, and is
recapitulated in vivo using antagonists for CB1R. We aim to investigate CBR signaling as a potential
therapeutic direction in response to alcohol and cannabinoid-dependent pulmonary inflammation.
Public Health Relevance Statement
Narrative:
Alcohol and cannabis consumption occur significantly in the world’s
population, and polysubstance misuse by adolescents may have significant long-term
effects on cognitive and other biological systems. Alcohol intoxication has been
linked to immune dis-regulation in the brain, liver and lung. Currently, contributing
effects of alcohol and cannabis adolescent exposure upon lung inflammation and
pneumonia remain unclear. Directed therapeutics can then be developed from these
mechanistic studies, to improve the health, vitality and productivity of alcohol and/or
cannabis-exposed people in our society.
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